Abstract (Overall): This new application from the University of Pittsburgh is for an O'Brien Urology Cooperative Research Center Grant to elucidate Molecular mechanisms of benign prostatic hyperplasia (BPH) and related lower urinary tract symptoms (LUTS). The Center investigators have expertise in an array of fields, including urology endocrinology, molecular biology, pharmacology, physiology, neuroscience, genetics and pathology. Using their various expertise, investigators developed multidisciplinary projects that contain basic mechanistic components as well as the use of human clinical specimens to study BPH/LUTS. The following proposed projects will address important factors involved in BPH/LUTS, with a focus on inflammation: Project 1: Afferent and urothelial plasticity underlying bladder sensitization in prostatic inflammation (Naoki Yoshimura); Project 2: Prostate luminal epithelial permeability and inflammation in BPH pathogenesis (Zhou Wang); Project 3: Impact of Cox-2 on protective effects of estrogen receptor beta in prostate epithelial cells (Donald DeFranco). The O'Brien Center has established an Administrative Core and a Tissue Resource and Morphology Core (TRMC) to increase synergy and efficiency. The Administrative Core, which includes an Executive Committee, an Internal Advisory Committee, and an External Advisory Committee, will provide strong administrative support through project review, pilot project selection and monitoring, opportunity pool program, educational enrichment, biostatistics analysis, clinical relevance review, and communication with general public. TRMC will provide human tissue specimens, morphology support, and animal tissue processing and distribution. Together, these Cores will help to both integrate the O'Brien Center into the University community by serving as a resource and to attract new investigators to the field of BPH.